Male fertility and sperm health
Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Medication
Sperm production falls during use
Linked to sharply lower sperm counts during use. In a prospective study, 77% of men fell below 40 million sperm, and pooled studies found lower counts than in non-users.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In 100 men followed through a self-chosen steroid cycle, 77% had a total sperm count below 40 million during use [6]. Pooled studies measuring men before and during use found luteinizing hormone fell 3.37 IU/L (95% CI -5.05 to -1.70), and follicle-stimulating hormone fell 1.73 IU/L (95% CI -2.67 to -0.79), and the review reported structural and functional sperm changes [5]. Against non-users, users had total sperm counts 47.28 million lower (95% CI -79.93 to -14.62) and fewer normally shaped sperm (SMD -2.00), while concentration did not differ significantly (-39.59 million/mL, 95% CI -82.82 to 3.63) [4].
- Population
- 100 male amateur strength athletes in the Netherlands [6]; 33 studies of 1,766 users and 2,113 non-users, mostly men [5]; men in 24 studies [4].
- Sources
- [6], [5], [4]
- Caveats
- Evidence comes from cohorts, cross-sectional studies and case series of users, who chose their own compounds and amounts. Few studies measured semen.
Slow and sometimes incomplete sperm recovery after stopping
Linked to sperm recovery taking about a year or longer after stopping. In one prospective study, a third of men still had low counts a year after starting.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Three months after a cycle ended, total sperm count was 61.7 million below baseline (95% CI 33.7 to 90.0). One year after the cycle began, it was still 29.7 million below baseline, and 34% of men had a total count under 40 million [6]. In current and past users compared with non-users, mean recovery time was 14.1 months for sperm output and 10.7 months for LH, and longer use was linked to slower sperm recovery. Past users did not differ from non-users except for smaller testes [7]. In 1,549 healthy men given testosterone-based contraceptive regimens in medical trials, sperm concentration recovered to 20 million/mL in 67% within 6 months, 90% within 12, 96% within 16 and 100% within 24 [8].
- Population
- 100 male amateur athletes [6]; 41 current and 31 past users and 21 non-users [7]; 1,549 healthy men in 30 contraceptive studies [8].
- Sources
- [6], [7], [8]
- Caveats
- Follow-up after the cycle was short in the prospective study [6]. The contraceptive data come from supervised medical doses and may understate recovery time after non-prescribed use of several compounds [8]. Recruitment through social media may select users [7].
Smaller testicles
Linked to smaller testicles in users and in former users years after stopping, in pooled and cross-sectional studies.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Pooled studies reported a reduction in testicular volume with steroid use [5]. Untreated former long-term users had testes 2.3 mL smaller than non-using weightlifters (95% CI 0.1 to 4.5) after 3 to 26 months off steroids [9]. Past users had residual smaller testis volume when other measures had recovered [7]. In 88 users and 68 non-users, users had shorter mean testicular length [10].
- Population
- Users in 33 studies [5]; 19 untreated former users and 36 non-using weightlifters [9]; 31 past users and 21 non-users [7]; 156 athletes [10].
- Sources
- [5], [9], [7], [10]
- Caveats
- Cross-sectional comparisons cannot show how volume changed in each man.
Sperm count and semen measures in healthy men
Mixed results: 1 mg did not change sperm in one trial. At 5 mg, total sperm count fell 34% at 26 weeks and was not significantly lower at 52.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In 181 men aged 19 to 41 given 1 mg finasteride or placebo for 48 weeks, sperm concentration, total sperm per ejaculate, motility and morphology did not change in the 79 men giving serial samples. Ejaculate volume fell 0.3 mL (11%) on finasteride against 0.2 mL (8%) on placebo [16]. In 99 healthy men given 5 mg finasteride, 0.5 mg dutasteride or placebo for a year, total sperm count on finasteride was 34.3% below baseline at 26 weeks, 16.2% below at 52 weeks (not significant) and 6.2% below 24 weeks after stopping. Motility fell 6% to 12% on both drugs, during treatment and at follow-up, and morphology did not change [17].
- Population
- 181 men aged 19 to 41, 79 of them in the semen subset [16]; 99 healthy men, 34 on finasteride [17].
- Sources
- [16], [17]
- Caveats
- The trials used different doses. 5 mg is the prostate dose, 5 times the hair loss dose. Neither trial measured pregnancy.
Low sperm counts in men seen for infertility
Case reports: in 27 men on finasteride at a fertility clinic, sperm counts rose an average 11.6-fold after stopping. The label lists male infertility among postmarketing reports.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Of 4,400 men seen for fertility evaluation, 27 (0.6%) were taking finasteride, for a mean 57.4 months at a mean 1.04 mg a day. After they stopped, sperm counts rose an average 11.6-fold, and 57% of men with counts below 5 million per mL rose above 15 million per mL. No man's count fell, and hormones, motility and morphology did not change [18]. The current Propecia label lists male infertility and/or poor seminal quality among postmarketing reports, and states that normalization or improvement of seminal quality has been reported after stopping [10].
- Population
- 27 men at a male infertility clinic, 2008 to 2012 [18]; postmarketing reports [10].
- Sources
- [18], [10]
- Caveats
- No control group, and men at an infertility clinic may differ from other users. Case series and postmarketing reports cannot give a rate.
Hormone therapy
Lower sperm production and fertility
Shown to stop sperm production in 65% of healthy men at contraceptive doses. Sperm recovered in 90% within 12 months and all within 24 months of stopping.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In 271 healthy fertile men given 200 mg testosterone enanthate weekly, 65% had no sperm in three consecutive samples by 6 months, after a mean of 120 days. After injections stopped, the median time to a sperm concentration of at least 20 million per mL was 3.7 months [19]. Across 30 studies of 1,549 men on testosterone alone or with a progestogen, the probability of sperm recovering to 20 million per mL was 67% within 6 months, 90% within 12 months, 96% within 16 months and 100% within 24 months of stopping. Recovery was slower after longer treatment and longer-acting testosterone preparations [20].
- Population
- Healthy men aged 18 to 51 with normal testosterone, studied as male contraception [19][20].
- Sources
- [19], [20]
- Caveats
- These are contraception studies in men with normal testosterone, at doses chosen to stop sperm production. They do not report rates for men treated for low testosterone. The pooled analysis includes regimens that added a progestogen [20].
Sperm and hormones in anabolic steroid users
Linked to lower sperm motility, smaller testes and suppressed FSH and LH in anabolic steroid users. FSH and LH matched nonusers about a year after stopping.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Across 32 studies (9,371 men, 2,671 of them users), anabolic-androgenic steroid users had lower FSH and LH than nonusers. These stayed low 3 to 6 months after stopping and did not differ from nonusers at 1 year. Sperm concentration was similar, while sperm motility was lower and testes were smaller in users. Total testosterone was lower in former users at 1 year [25].
- Population
- 12 cohort studies, 5 case-control studies, 9 cross-sectional surveys and 6 case reports of men using supraphysiologic doses for sport or appearance [25].
- Sources
- [25]
- Caveats
- Observational studies, most of them small, with several drugs often used together, little dosing information and high heterogeneity [25].
Sperm recovery in men seen for infertility while on testosterone
Case reports: of 49 men with no or very few sperm while on testosterone, 47 regained sperm on hCG-based treatment, after a mean of 4.6 months.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- At two US infertility clinics, 49 men presented with azoospermia or fewer than 1 million sperm per mL while taking testosterone. On 3,000 units of hCG every other day with clomiphene, tamoxifen, anastrozole or FSH, sperm returned or counts improved in 47 (95.9%), and one more man had a documented pregnancy. Mean time to return was 4.6 months, with a mean first concentration of 22.6 million per mL. No man stopped treatment because of adverse events [24].
- Population
- 49 men in a retrospective case series [24].
- Sources
- [24]
- Caveats
- No comparison group, so it cannot show how many men recover after stopping testosterone without treatment. Chart review of men who came to infertility clinics, so it gives no rate of suppression among all men on testosterone [24].
Supplements
Male fertility and semen quality
Shown to raise sperm count and motility in men with unexplained infertility. Reviews disagree on sperm concentration and on the size of the effect.
The numbers and sources
- Effect
- In 9 studies (781 men) with idiopathic infertility, CoQ10 raised sperm concentration by 10.22 million/mL (95% CI 3.51 to 16.93) and total motility by 4.95 percentage points (95% CI 1.15 to 8.75), and raised the odds of clinical pregnancy (OR 6.02, 95% CI 1.97 to 18.41) [21]. In 8 RCTs (877 men), total sperm count, total and progressive motility and normal morphology were higher on CoQ10, and sperm concentration and semen volume did not change [22]. A network meta-analysis of 16 studies in men with unexplained infertility found CoQ10 improved sperm concentration over placebo [23].
- Population
- Men with idiopathic or unexplained infertility [21][23]; men in RCTs of semen quality [22].
- Sources
- [21], [22], [23]
- Caveats
- One review reported standardized mean differences as large as 13.38, several times the 2.98 reported by the network meta-analysis [23], with significant heterogeneity between studies [22]. The pregnancy interval is wide [21]. The reviews disagree on sperm concentration [21][22].
Sperm motility and shape in infertile men
Shown in two reviews to raise sperm motility about 10 percentage points and normal sperm shape slightly in men with idiopathic infertility. Sperm concentration did not change.
Compared with placebo or no treatment [14]; placebo [15]
The numbers and sources
- Effect
- Across 7 RCTs (459 men), carnitines raised total sperm motility by 10.72 percentage points (95% CI 3.94 to 17.50), and across 3 RCTs progressive motility by 9.82 points (95% CI 2.01 to 17.62). Across 6 RCTs (438 men), normal morphology rose 2.41 points (95% CI 0.79 to 4.03) and sperm concentration did not change (MD 2.70 million per mL, 95% CI -2.04 to 7.44) [14]. In men with idiopathic asthenozoospermia, L-carnitine or acetyl-L-carnitine raised motility (MD 9.48, 95% CI 0.95 to 18.01, 4 RCTs, 190 men) and normal morphology (MD 4.89, 95% CI 1.40 to 8.39, 2 RCTs, 139 men) and did not change concentration [15].
- Population
- 8 RCTs in men with idiopathic infertility, published 2000 to 2020 [14]; men with idiopathic asthenozoospermia in 7 studies with 621 men, some testing NAC [15].
- Sources
- [14], [15]
- Caveats
- Heterogeneity was high (I² 94% to 97%) and certainty was rated low or very low [14]. The two reviews share trials. Sperm measures are not pregnancy or live birth.
Sperm motility in infertile men
Shown in one review of 3 trials to raise sperm motility in infertile men taking DHA or EPA. Sperm concentration did not change.
Compared with control groups in 3 RCTs [56]; placebo, no supplement or lower intake, in trials and observational studies [57]
The numbers and sources
- Effect
- Across 3 RCTs (147 men on omega-3, 143 controls), DHA or EPA, alone or with other micronutrients, raised sperm motility (printed as RR 5.82, 95% CI 2.91 to 8.72, I² 76%) and seminal plasma DHA, and did not change sperm concentration (printed as RR 0.31, 95% CI -8.13 to 8.76) [56]. A systematic review of 16 trials and observational studies found 14 reported an improvement in, or a link with, at least one semen measure. It pooled no data because the studies differed too much [57].
- Population
- 290 infertile men in 3 RCTs [56]; infertile and fertile men in 16 studies [57].
- Sources
- [56], [57]
- Caveats
- Three small trials with high heterogeneity. The review labels its pooled values risk ratios, though a ratio cannot have a negative bound such as -8.13, so they read as mean differences [56]. The systematic review mixed trials with observational studies [57]. Sperm measures are not pregnancy or live birth.
Sperm count and semen quality
Shown in one pooled analysis of four small studies to raise sperm concentration slightly. Total and progressive motility, sperm shape and DNA damage did not change in the pooled data.
Compared with placebo, or the same men before supplementing in one uncontrolled study, across the four pooled studies [1]; placebo [2][3]; before supplementing, in the same men [4]
The numbers and sources
- Effect
- Across 4 studies of 151 men, lycopene raised sperm concentration (SMD 0.33, 95% CI 0.02 to 0.65) and nonprogressive motility (SMD 0.45, 95% CI 0.04 to 0.87). Total motility, progressive motility, normal or abnormal morphology, semen volume and DNA damage did not change [1]. In 44 men with low sperm counts, 12 weeks of lycopene raised total sperm count and concentration against placebo [2]. In 56 healthy young men, 12 weeks of lactolycopene did not change the primary outcome, motile sperm concentration (p = 0.058), and raised the share of fast progressive sperm (p = 0.006) and normally shaped sperm (p < 0.001) against placebo [3]. In an uncontrolled study of 30 infertile men, concentration rose in 20 (66%) and motility in 16 (53%) after 3 months [4].
- Population
- 151 men in 4 studies, healthy or infertile, aged on average 23 to 38 [1]; 44 infertile men with oligozoospermia [2]; 60 healthy men randomized, 56 completing [3]; 30 men with idiopathic infertility [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- Four small studies, one without a control group [4]. The pooled analysis noted publication bias and methodological heterogeneity [1]. The trials disagree on which measures changed: the healthy-men trial found shape and fast motility improved and the pooled analysis did not [1][3]. Semen measures are not pregnancies.
Male fertility and semen quality
Shown to improve sperm concentration, motility, morphology and semen volume in men with infertility, measured as semen quality rather than pregnancy.
The numbers and sources
- Effect
- Across 5 RCTs in men with infertility or impaired semen, NAC raised semen volume (MD 0.69 mL), sperm concentration (MD 4.43), total motility (MD 9.69) and normal morphology (MD 1.36) against control [8]. In 3 placebo-controlled trials in idiopathic male infertility, NAC improved sperm concentration, morphology, motility and ejaculation volume [9].
- Population
- Men with infertility or impaired semen parameters [8][9].
- Sources
- [8], [9]
- Caveats
- Few trials, likely overlapping between the reviews. Semen measures, not pregnancy or live birth. The abstract of [9] reports p-values only.
Sperm motility and shape, zinc alone
Shown in one review to raise semen volume, sperm motility and normal sperm shape in infertile men, measured before and after zinc in the same men.
Compared with before zinc, in the same men [23]
The numbers and sources
- Effect
- Pooling studies of zinc given to infertile men, the review found zinc raised semen volume, sperm motility and the share of normally shaped sperm, printed as SMD -0.99 (95% CI -1.60 to -0.38), -1.82 (95% CI -2.63 to -1.01) and -0.75 (95% CI -1.37 to -0.14). Sperm concentration, count and viability did not change. Three of the six studies listed used 220 mg zinc sulfate a day, and one used 66 mg [23].
- Population
- Infertile men in 6 supplementation studies, within a review of 20 studies [23].
- Sources
- [23]
- Caveats
- Each study compared men before and after zinc, so the review has no placebo comparison. The review prints these increases as negative SMDs. Sperm measures are not pregnancy or live birth.
Sperm count in men with low sperm counts
One trial of 46 men with low sperm counts found sperm count rose 167% from baseline after 90 days of ashwagandha, with little change on placebo.
Compared with placebo [21]
The numbers and sources
- Effect
- 675 mg a day of a full-spectrum root extract for 90 days raised sperm count from 9.59 to 25.61 million per mL (167%), semen volume from 1.74 to 2.76 mL (53%) and motility from 18.62% to 29.19% (57%) from baseline (P < 0.0001 for each), with minimal change on placebo. Serum testosterone rose 17% (4.45 to 5.22 ng/mL) and LH 34% from baseline [21].
- Population
- 46 men with sperm counts below 20 million per mL, 21 on ashwagandha and 25 on placebo [21].
- Sources
- [21]
- Caveats
- One small pilot trial. Changes are reported from baseline within each group. It tested one branded extract (KSM-66, Ixoreal Biomed). Pregnancy was not measured [21].
Semen volume and testis size in young men using fish oil
One study linked fish oil use on 60 or more days to 0.64 mL more semen and 1.5 mL larger testes in 1,679 young Danish men, observationally.
Compared with men who took no supplements [58]
The numbers and sources
- Effect
- Of 1,679 men, 98 (5.8%) had used fish oil in the past 3 months. After adjustment, use on 60 or more days was linked to 0.64 mL higher semen volume (95% CI 0.15 to 1.12) and 1.5 mL larger testes (95% CI 0.2 to 2.8). Fish oil users had 20% lower FSH and 16% lower LH. No other supplement was linked to testicular function [58].
- Population
- 1,679 men with a median age of 18.9, recruited at military fitness examinations in Denmark, 2012 to 2017 [58].
- Sources
- [58]
- Caveats
- Cross-sectional, so it cannot show cause. The omega-3 content of the supplements was not measured [58]. Pregnancy was not measured.
Semen quality in men with idiopathic infertility
Limited evidence: one study without a control group found semen measures improved in the 75 of 350 men with idiopathic infertility who completed 3 months.
Compared with before the extract, in the same men [10]
The numbers and sources
- Effect
- 350 male partners of subfertile couples took 200 mg a day of a proprietary water-soluble root extract, with semen analysis every 3 months for 9 months. In the 75 who completed one 3-month cycle, semen volume, sperm concentration, normal morphology and motility all improved significantly, and 11 couples (14.7%) had spontaneous pregnancies [10].
- Population
- 75 of 350 men with idiopathic infertility who completed 3 months [10].
- Sources
- [10]
- Caveats
- No control group, so the change cannot be separated from time or retesting, and 275 of the 350 men did not complete a 3-month cycle. The abstract gives no effect sizes and does not state funding [10].
Sperm quality, folic acid taken by men
Mixed results: one review found folic acid alone raised sperm motility about 3.6 points in infertile men, while folic acid with zinc changed no sperm measure.
Compared with controls in 8 RCTs [25]; placebo [26]
The numbers and sources
- Effect
- Across 8 RCTs (2,168 men), folic acid alone raised sperm motility (MD 3.63, 95% CI -1.22 to 6.05, P = 0.003) and did not change sperm concentration (MD 2.53, 95% CI -1.68 to 6.73) or morphology (MD -0.02, 95% CI -0.29 to 0.24). Folic acid plus zinc did not change concentration (MD 1.87), motility (MD 1.67) or morphology (MD -0.05) [25]. In the FAZST trial, 5 mg folic acid with 30 mg zinc daily for 6 months did not change sperm concentration, motility, morphology, volume or total motile count against placebo in 1,629 men [26].
- Population
- 8 RCTs with 2,168 infertile men [25]; 1,629 men with semen analyzed, of 2,370 randomized [26].
- Sources
- [25], [26]
- Caveats
- The motility interval printed in [25] crosses zero though its P value is 0.003. It is given here as printed. FAZST supplied 1,629 of the review's 2,168 men [25]. Sperm measures are not pregnancy or live birth.
Pregnancy and live birth when the male partner takes antioxidants
Mixed results: a Cochrane review of antioxidants for subfertile men found more pregnancies and live births, while a selenium, carnitine and CoQ10 review and a combination trial did not.
Compared with placebo or no treatment [17]; placebo [18][19]
The numbers and sources
- Effect
- In a Cochrane review, antioxidants taken by subfertile men were linked to more live births (OR 1.43, 95% CI 1.07 to 1.91, 12 RCTs, 1,283 men, very low certainty) and more clinical pregnancies (OR 1.89, 95% CI 1.45 to 2.47, 20 RCTs, 1,706 men, low certainty). With trials at high risk of bias removed, live birth no longer differed (Peto OR 1.22, 95% CI 0.85 to 1.75, 8 RCTs) [17]. In a review of 20 randomized studies of selenium, carnitine or CoQ10, alone or combined, pregnancy occurred in 69 of 426 couples (16.2%) on treatment and 45 of 401 (11.2%) on placebo (P = .05), which the authors report as no difference [18]. In the MOXI trial, a daily combination including 0.20 mg selenium gave a cumulative live birth rate of 15% against 24% on placebo at 6 months [19].
- Population
- 90 RCTs with 10,303 subfertile men aged 18 to 65 [17]; couples with idiopathic male infertility in 20 randomized studies [18]; 174 men with male factor infertility at 9 US fertility centers [19].
- Sources
- [17], [18], [19]
- Caveats
- The Cochrane review pooled 20 different antioxidants and combinations, so it does not isolate selenium, and most trials were small [17]. [18] rated study quality poor. MOXI combined selenium with vitamins C and E, L-carnitine, zinc, folic acid and lycopene [19].
Pregnancy and live birth when the male partner takes antioxidants
Mixed results: two reviews of antioxidant supplements, vitamin C among them, found more pregnancies in couples, while live births rose in one review and not in a 174-man trial.
Compared with placebo or no treatment [29][30]; placebo [31]
The numbers and sources
- Effect
- In a Cochrane review, antioxidants taken by subfertile men were linked to more live births (OR 1.43, 95% CI 1.07 to 1.91, 12 RCTs, 1,283 men, very low certainty) and more clinical pregnancies (OR 1.89, 95% CI 1.45 to 2.47, 20 RCTs, 1,706 men, low certainty). With trials at high risk of bias removed, live birth no longer differed (Peto OR 1.22, 95% CI 0.85 to 1.75, 8 RCTs) [29]. A second review found more spontaneous pregnancies (OR 1.97, 95% CI 1.28 to 3.04, 16 RCTs, 1,355 men) and no change in live birth (OR 1.21, 95% CI 0.53 to 2.76, 4 RCTs, 388 men) [30]. In the MOXI trial, a daily combination including 500 mg vitamin C gave a cumulative live birth rate of 15% against 24% on placebo at 6 months [31].
- Population
- 90 RCTs with 10,303 subfertile men aged 18 to 65 [29]; 45 RCTs with 4,332 infertile men [30]; 174 men with male factor infertility at 9 US fertility centers [31].
- Sources
- [29], [30], [31]
- Caveats
- The reviews pool many different antioxidants and combinations, so they do not isolate vitamin C. Most trials were small, and few reported live birth [29]. MOXI combined vitamin C with vitamin E, selenium, L-carnitine, zinc, folic acid and lycopene [31].
Sperm count, motility and shape
Mixed results: one review found slightly higher sperm motility, concentration and normal shape in infertile men on vitamin C or E, while a 174-man combination trial found none.
Compared with control groups the source's abstract does not describe [32]; placebo [33][31]
The numbers and sources
- Effect
- Across 11 RCTs (832 men), vitamin E and vitamin C raised progressive motility (SMD 0.38, 95% CI 0.22 to 0.55), sperm concentration (SMD 0.21, 95% CI 0.09 to 0.34), normal morphology (SMD 0.32, 95% CI 0.09 to 0.55) and total sperm number (SMD 0.28, 95% CI 0.12 to 0.43) against control, with no adverse effects reported [32]. In 115 infertile men after varicocele surgery, 250 mg vitamin C twice a day for 3 months raised motility (P = 0.016) and normal morphology (P < 0.001) over placebo, and sperm count did not differ (P = 0.091) [33]. In MOXI, motility, morphology and DNA fragmentation did not differ from placebo after 3 months, and sperm concentration changed by a median -4.0 million per mL on the combination against +2.4 million per mL on placebo [31].
- Population
- 832 infertile men in 11 RCTs [32]; 115 infertile men with varicocele, mean age 27.6 [33]; 174 men with male factor infertility [31].
- Sources
- [32], [33], [31]
- Caveats
- The review pooled vitamin C and vitamin E trials and rated the evidence moderate to low [32]. The standardized effects are small. Sperm measures are not pregnancy or live birth.
Sperm DNA fragmentation
Mixed results: one 64-man trial found DNA-damaged sperm fell from 22% to 9% on vitamins C and E, while a review and a combination trial found no change.
Compared with placebo [34][31]; placebo or no treatment [30]
The numbers and sources
- Effect
- In 64 men with unexplained infertility and 15% or more DNA-fragmented sperm, 1 g vitamin C and 1 g vitamin E daily for 2 months lowered fragmented sperm from 22.1% to 9.1% (P < .001), with no change on placebo and no change in basic sperm parameters [34]. Among 44 MOXI men with high DNA fragmentation, fragmentation at 3 months was a median 29.5% on the combination and 28.0% on placebo [31]. A review found no effect on sperm DNA fragmentation across 3 trials [30].
- Population
- 64 men with unexplained infertility [34]; 44 men with high DNA fragmentation within a 174-man trial [31]; 3 RCTs within a review of 45 [30].
- Sources
- [34], [31], [30]
- Caveats
- The positive trial was small and measured fragmentation with one assay (TUNEL) [34]. DNA fragmentation is a sperm measure, not pregnancy or live birth.
Sperm motility and semen quality in infertile men
Mixed results: two reviews found sperm motility rose about 4 to 7 points on vitamin D in infertile men, while the largest trial, 330 men, found no change.
Compared with placebo [74][76]; control groups in 8 RCTs and 3 observational studies [75]
The numbers and sources
- Effect
- Across 5 RCTs (648 men), vitamin D raised total motility (MD 4.96, 95% CI 0.38 to 9.54), progressive motility (MD 4.14, 95% CI 0.25 to 8.02) and normal morphology (MD 0.44, 95% CI 0.30 to 0.57), and did not change total count, concentration or semen volume [74]. Across 11 studies (1,168 men), progressive motility rose (MD 6.96 points), sperm concentration rose (MD 3.74 million per mL) and semen volume rose (MD 0.36 mL) [75]. In 330 infertile men with 25OHD of 50 nmol/L or below, 300,000 IU once and then 1,400 IU with 500 mg calcium daily for 150 days did not change semen parameters against placebo [76].
- Population
- 648 infertile men in 5 RCTs [74]; 1,168 infertile men in 8 RCTs and 3 observational studies [75]; 330 infertile men in Copenhagen [76].
- Sources
- [74], [75], [76]
- Caveats
- Heterogeneity was high for motility (I² 69% and 89%) [74]. One study carried 82% of the weight for sperm concentration in [75], which also pools the 330-man trial. Sperm measures are not pregnancy or live birth.
Pregnancy and live birth when the male partner takes vitamin E
Mixed results: one review found pregnancy rates 1.86 times higher with vitamin E, and one IVF trial more live births, while a combination trial found no gain.
Compared with control groups the source's abstract does not describe [24]; placebo [25][26]
The numbers and sources
- Effect
- Across RCTs of vitamin E and vitamin C in infertile men, the pregnancy rate was higher in the vitamin E group than in control (RR 1.86, 95% CI 1.02 to 3.41) [24]. In 101 couples undergoing IVF, 400 mg vitamin E daily for 3 months gave live births in 17 of 41 transfers (41.5%) against 9 of 44 (20.5%) on placebo. Clinical pregnancy per transfer (43.9% against 25%) and implantation (24.7% against 14.1%) were higher but not significantly [25]. In the MOXI trial, a daily combination including 400 mg vitamin E gave a cumulative live birth rate of 15% against 24% on placebo at 6 months [26].
- Population
- 832 infertile men in 11 RCTs [24]; 101 couples undergoing IVF, 64.4% of the men with an abnormal semen analysis [25]; 174 men with male factor infertility at 9 US fertility centers [26].
- Sources
- [24], [25], [26]
- Caveats
- The review rated its evidence moderate to low [24]. The live birth result in [25] was counted per transfer, in one trial. MOXI combined vitamin E with vitamin C, selenium, L-carnitine, zinc, folic acid and lycopene [26].
Sperm count, motility and shape
Mixed results: two reviews found total sperm count rose slightly with vitamin E, while concentration and motility rose in one review only. A 101-man trial found no gain over placebo.
Compared with control groups in 8 RCTs the abstract does not describe [27]; control groups the source's abstract does not describe [24]; placebo [25]
The numbers and sources
- Effect
- Across 8 RCTs (459 men), vitamin E raised total sperm count (SMD 0.23, 95% CI 0.02 to 0.45) and lowered semen volume (SMD -0.30, 95% CI -0.55 to -0.06), and did not change sperm concentration (SMD 0.04, 95% CI -0.21 to 0.29) or total motility (SMD 0.20, 95% CI -0.01 to 0.42). Forward motility rose in trials lasting 6 months (SMD 0.80, 95% CI 0.46 to 1.14) [27]. Across 11 RCTs (832 men) of vitamin E and vitamin C, progressive motility (SMD 0.38), concentration (SMD 0.21), normal morphology (SMD 0.32) and total sperm number (SMD 0.28) rose against control [24]. In 101 men in couples undergoing IVF, 400 mg a day for 3 months did not improve sperm measures over placebo, and normal morphology was higher on placebo [25].
- Population
- 459 infertile men in 8 RCTs [27]; 832 infertile men in 11 RCTs [24]; 101 men in couples undergoing IVF [25].
- Sources
- [27], [24], [25]
- Caveats
- The authors of [27] suggest the lower semen volume may reflect different abstinence times before testing. The standardized effects are small. Sperm measures are not pregnancy or live birth.
Sperm DNA fragmentation with folic acid and zinc
One 2,370-couple trial found sperm DNA fragmentation slightly higher on folic acid with zinc, a mean 29.7% against 27.2% on placebo.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- At 6 months, mean sperm DNA fragmentation was 29.7% on 5 mg folic acid and 30 mg zinc daily against 27.2% on placebo (mean difference 2.4%, 95% CI 0.5% to 4.4%) [26].
- Population
- 1,629 men with semen analyzed at 6 months, of 2,370 randomized [26].
- Sources
- [26]
- Caveats
- One trial, testing folic acid and zinc together. Live birth did not differ between groups [26].
- Why limited
- This rests on one trial, of 2,370 people. Strength counts independent studies that agree, so one trial is limited at any size.
Sperm motility and count, selenium alone
Limited evidence: one 69-man trial found sperm motility rose on selenium in subfertile men, while a 33-man study found no change in count, motility or shape.
Compared with placebo [20]; before supplementation, in the same men [21]
The numbers and sources
- Effect
- In 69 subfertile men with low sperm motility, 3 months of selenium alone or with vitamins A, C and E raised plasma selenium and sperm motility against placebo (P = 0.023, with the two selenium groups combined) and did not change sperm density. Five men (11%) on selenium achieved paternity against none on placebo, and 56% of treated men responded [20]. In 33 subfertile men given 200 µg a day as selenium yeast or sodium selenite for 12 weeks, seminal selenium rose while sperm count, motility and morphology did not change [21].
- Population
- 69 men attending a subfertility clinic in the West of Scotland [20]; 33 subfertile men [21].
- Sources
- [20], [21]
- Caveats
- Both studies are small. The motility result in [20] was significant only after the two selenium groups were combined. [21] had no placebo group.
Lower sperm motility on a high-selenium diet
One 11-man study found the share of motile sperm ended 18% below baseline on a diet of about 300 µg selenium a day for 99 days.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Eleven healthy men lived in a metabolic research unit for 120 days on foods naturally high or low in selenium: 47 µg a day for 21 days, then 297 µg or 13 µg a day for 99 days. Seminal plasma selenium rose 50% on the high intake. On the high intake, the fraction of motile sperm fell 32% by week 13 and ended 18% below baseline. Serum androgens did not change, while T3 fell and TSH rose in the high-selenium group [22].
- Population
- 11 healthy men, randomized to high or low selenium foods [22].
- Sources
- [22]
- Caveats
- Eleven men, with selenium from food rather than supplements. The authors note that lower motility does not necessarily predict lower fertility [22].
Sperm DNA fragmentation
Limited evidence: one 64-man trial found DNA-damaged sperm fell from 22% to 9% on vitamins C and E, while a combination trial found no change.
Compared with placebo [28][26]
The numbers and sources
- Effect
- In 64 men with unexplained infertility and 15% or more DNA-fragmented sperm, 1 g vitamin C and 1 g vitamin E daily for 2 months lowered fragmented sperm from 22.1% to 9.1% (P < .001), with no change on placebo and no change in basic sperm parameters [28]. Among 44 MOXI men with high DNA fragmentation, fragmentation at 3 months was a median 29.5% on the combination and 28.0% on placebo [26].
- Population
- 64 men with unexplained infertility [28]; 44 men with high DNA fragmentation within a 174-man trial [26].
- Sources
- [28], [26]
- Caveats
- Neither trial tested vitamin E alone. The positive trial was small and measured fragmentation with one assay (TUNEL) [28]. DNA fragmentation is a sperm measure, not pregnancy or live birth.
Sperm DNA fragmentation with zinc and folic acid
One 2,370-couple trial found sperm DNA fragmentation slightly higher on zinc with folic acid, a mean 29.7% against 27.2% on placebo.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- At 6 months, mean sperm DNA fragmentation was 29.7% on 30 mg zinc and 5 mg folic acid daily against 27.2% on placebo (mean difference 2.4%, 95% CI 0.5% to 4.4%) [24].
- Population
- 1,629 men with semen analyzed at 6 months, of 2,370 randomized [24].
- Sources
- [24]
- Caveats
- One trial, testing zinc and folic acid together. Live birth did not differ between groups [24].
- Why limited
- This rests on one trial, of 2,370 people. Strength counts independent studies that agree, so one trial is limited at any size.
Pregnancy and live birth when the male partner takes folic acid
Not shown to raise live birth or pregnancy rates when the male partner took folic acid with or without zinc, in a 2,370-couple trial and a review.
Compared with placebo [26][25]
The numbers and sources
- Effect
- In FAZST, live births were 404 (34%) on folic acid with zinc against 416 (35%) on placebo (risk difference -0.9%, 95% CI -4.7% to 2.8%) [26]. In the review, clinical pregnancy per embryo transfer was 35.6% with folic acid alone against 20.4% on placebo (P = 0.082), and folic acid plus zinc did not affect pregnancy outcomes [25].
- Population
- 2,370 couples at 4 US fertility centers, men with a mean age of 33 [26]; 8 RCTs in infertile men [25].
- Sources
- [26], [25]
- Caveats
- The folic acid alone pregnancy result comes from one IVF trial within the review [25]. FAZST enrolled men from couples seeking treatment, not only men with abnormal semen [26].
Pregnancy in couples when the male partner takes carnitine
Not shown to raise clinical pregnancy rates when the male partner took carnitine, in two reviews of small trials. No live birth data were pooled.
Compared with placebo or no treatment [14]; placebo [16]
The numbers and sources
- Effect
- Across 4 RCTs (252 couples), clinical pregnancy did not differ from control (RR 1.17, 95% CI 0.55 to 2.46) [14]. In a review of 20 randomized studies of selenium, carnitine or CoQ10, alone or combined, pregnancy occurred in 69 of 426 couples (16.2%) on treatment and 45 of 401 (11.2%) on placebo (P = .05), which the authors report as no difference [16].
- Population
- Couples in 4 RCTs of men with idiopathic infertility [14]; couples with idiopathic male infertility in 20 randomized studies [16].
- Sources
- [14], [16]
- Caveats
- Few pregnancies and small trials. [16] pools carnitine with selenium and CoQ10 and rated study quality poor.
Semen quality
Not shown to raise sperm concentration against placebo, with mixed effects on other semen measures in infertile and healthy men.
The numbers and sources
- Effect
- In a meta-analysis of 5 RCTs, maca did not raise sperm concentration compared with placebo (mean difference 2.22, 95% CI -2.94 to 7.37, p = 0.4). Effects on other semen measures were mixed in infertile and healthy men [6].
- Population
- Infertile men and healthy men [6].
- Sources
- [6]
- Caveats
- Five small trials [6].
Live birth in couples, zinc with folic acid taken by the man
Not shown to raise live birth or pregnancy in couples seeking infertility treatment when the man took zinc with folic acid, in a 2,370-couple trial and a review.
Compared with placebo [24][25]
The numbers and sources
- Effect
- In the FAZST trial, men took 30 mg elemental zinc and 5 mg folic acid or placebo daily for 6 months. Live births were 404 (34%) against 416 (35%) on placebo (risk difference -0.9%, 95% CI -4.7% to 2.8%) [24]. A meta-analysis of 8 RCTs (2,168 men) found folic acid plus zinc did not affect pregnancy outcomes [25].
- Population
- 2,370 couples at 4 US fertility centers, men with a mean age of 33 and women aged 18 to 45 [24]; 8 RCTs in infertile men [25].
- Sources
- [24], [25]
- Caveats
- FAZST enrolled men from couples seeking treatment, not only men with abnormal semen [24]. FAZST supplied 1,629 of the 2,168 men in the meta-analysis [25].
Sperm count, motility and shape, zinc with folic acid
Not shown to change sperm concentration, motility or shape in men taking zinc with folic acid, in a 2,370-couple trial and a review of 8 trials.
Compared with placebo [24]; controls in 8 RCTs [25]
The numbers and sources
- Effect
- In FAZST, sperm concentration, motility, morphology, semen volume and total motile sperm count did not differ from placebo at 6 months among the 1,629 men with semen available [24]. Pooled, folic acid plus zinc did not change sperm concentration (MD 1.87, 95% CI -1.39 to 5.13), motility (MD 1.67, 95% CI -1.29 to 4.63) or morphology (MD -0.05, 95% CI -0.27 to 0.18) [25].
- Population
- 1,629 men with semen analyzed, of 2,370 randomized [24]; 8 RCTs with 2,168 infertile men [25].
- Sources
- [24], [25]
- Caveats
- The meta-analysis includes FAZST [25]. Sperm measures are not pregnancy or live birth.
Pregnancy and live birth
One trial of an antioxidant combination that included lycopene found no more live births than placebo. No trial has tested lycopene alone for pregnancy or live birth.
Compared with placebo, for a combination of seven antioxidants that included lycopene [5]; no comparison group, in an uncontrolled study [4]
The numbers and sources
- Effect
- In 171 couples with male factor infertility, the man taking an antioxidant combination (vitamins C and E, selenium, L-carnitine, zinc, folic acid and lycopene) for 3 to 6 months did not raise cumulative live birth against placebo (15% against 24%). Sperm motility, morphology and DNA fragmentation did not differ, and sperm concentration changed by a median of -4.0 million/mL on antioxidants and +2.4 million/mL on placebo [5]. In an uncontrolled study, 6 pregnancies occurred among the 26 men without severe oligospermia (23%) after 3 months of lycopene [4].
- Population
- 174 men with abnormal semen or high DNA fragmentation and their ovulating partners, at 9 US fertility centers [5]; 30 men with idiopathic infertility [4].
- Sources
- [5], [4]
- Caveats
- The trial tested a mixture, so lycopene's own effect cannot be separated, and it was limited by sample size [5]. The pregnancy count without a control group cannot show what lycopene added [4].
Pregnancy and live birth when the male partner takes vitamin D
Limited evidence: one review found no change in pregnancy or live birth, each pooled from 2 studies. One trial found more live births in a subgroup with low sperm counts.
Compared with control groups [75]; placebo [76]
The numbers and sources
- Effect
- Clinical pregnancy did not differ (RR 2.20, P = 0.61, 2 studies, I² 78%), and neither did live birth (RR 0.91, P = 0.77, 2 studies) [75]. In the 330-man trial, spontaneous pregnancies were 7.3% against 2.4% on placebo (difference 5.0%, 95% CI -0.6% to 10.5%). In the subgroup of men with low sperm counts, live births were 35.6% against 18.3% (difference 17.3%, 95% CI 1.6% to 32.9%) [76].
- Population
- Couples in 2 studies per outcome, within a review of 11 [75]; 330 infertile men with low vitamin D and their partners [76].
- Sources
- [75], [76]
- Caveats
- Two studies per pooled outcome, with high heterogeneity for pregnancy [75]. The live birth difference came from a subgroup of one trial [76].
Therapies
Sperm count and semen quality
Shown to raise sperm concentration against no treatment in infertile men with a palpable varicocele. Reviews disagree on whether motility and sperm shape also improve.
Compared with untreated infertile men with clinical varicocele [1]; observation [2]; before repair, in the same men [3]
The numbers and sources
- Effect
- Across 16 studies of 2,420 infertile men with clinical varicocele (1,424 repaired, 996 untreated), repaired men had higher sperm concentration (SMD 1.739, 95% CI 1.129 to 2.349), total sperm count (SMD 1.894), progressive motility (SMD 3.301), total motility (SMD 0.887, 95% CI 0.036 to 1.738) and normal morphology (SMD 1.673). Semen volume did not differ (SMD 0.313, 95% CI -0.242 to 0.868) [1]. Across 12 prospective studies (1,357 men), sperm concentration rose 12.34 million/mL more than with observation (95% CI 3.49 to 21.18), while progressive motility and normal morphology did not differ from observation. The benefit was seen in men with an abnormal semen analysis [2]. Across 22 prospective studies measuring the same men before and after repair, concentration rose 12.32 million/mL (95% CI 9.45 to 15.19) [3].
- Population
- Infertile men with a palpable (clinical) varicocele, in randomized and observational studies [1]; adult infertile men with any-grade varicocele in prospective trials [2]; men with clinical varicocele in prospective studies [3].
- Sources
- [1], [2], [3]
- Caveats
- These are semen measures, not pregnancies. Heterogeneity was very high (I² 97% to 98.5%) and publication bias was present for concentration and progressive motility [1]. Most included studies were at intermediate or high risk of bias [2]. Nobody can be blinded to surgery.
Pregnancy rates
Shown to raise pregnancy rates against no or delayed treatment in two reviews, at low certainty. An older review of four trials found no significant difference.
Compared with no treatment, delayed treatment or non-surgical care [4]; observation [2]; observation, in 4 randomized trials [3]
The numbers and sources
- Effect
- A Cochrane review found treatment may raise pregnancy rates against delayed or no treatment (RR 1.55, 95% CI 1.06 to 2.26; 13 RCTs, 1,193 couples; I² 65%; low certainty). Pregnancy was 21% without treatment and 22% to 48% after it [4]. A review of 12 prospective studies found more pregnancies than with observation (OR 1.29, 95% CI 1.00 to 1.65, p = 0.048) [2]. An earlier pooled analysis of 4 RCTs in men with low sperm counts found a nonsignificant difference (OR 2.23, 95% CI 0.86 to 5.78) [3].
- Population
- Couples in which the man had a varicocele and the female partner had no known fertility problem, in 48 RCTs with 5,384 participants overall [4]; adult infertile men [2]; men with low sperm counts [3].
- Sources
- [4], [2], [3]
- Caveats
- This block measured pregnancy, not live birth. The Cochrane reviewers rated certainty low because of risk of bias and inconsistency [4]. The lower confidence limit in one review sits at 1.00 [2].
Sperm in men with no sperm in the ejaculate (azoospermia)
Shown to raise sperm retrieval rates in men with nonobstructive azoospermia and a varicocele. About 44% had sperm in the ejaculate after repair.
Compared with men with nonobstructive azoospermia and varicocele without repair [6][5]; before repair, in the same men [6]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In 3 controlled studies, surgical sperm retrieval succeeded more often after repair than without it (OR 2.65, 95% CI 1.69 to 4.14). In 15 studies reporting semen after repair, 43.9% of men (range 20.8% to 55.0%) had sperm in the ejaculate [6]. A second review found higher sperm retrieval rates in men still azoospermic after repair (OR 2.509) [5].
- Population
- 468 men with nonobstructive azoospermia and clinical varicocele, treated by surgery or percutaneous embolization [6]; azoospermic men in assisted reproduction [5].
- Sources
- [6], [5]
- Caveats
- Only 3 controlled studies informed the retrieval estimate, and the evidence was rated low to moderate in quality [6]. The two reviews share studies, so their agreement is not fully independent.
Sperm DNA damage
Shown to lower sperm DNA fragmentation after repair in infertile men with a palpable varicocele, measured before and after in the same men.
Compared with before repair, in the same men [7][8]
The numbers and sources
- Effect
- Across 19 studies of 1,070 men, sperm DNA fragmentation was 7.23 percentage points lower after repair (95% CI -8.86 to -5.59; I² 91%), with larger drops in men whose fragmentation was high before surgery [7]. Across 29 studies of 1,491 men, fragmentation fell (SMD -1.125, 95% CI -1.410 to -0.840; I² 91%) and seminal malondialdehyde, a marker of oxidative stress, fell (SMD -2.450, 95% CI -3.903 to -0.997) [8].
- Population
- Infertile men with clinical varicocele [7][8].
- Sources
- [7], [8]
- Caveats
- Neither review compared repaired men with an untreated group, so changes over time without surgery cannot be excluded. Heterogeneity was high [7][8]. A lower fragmentation result is not a pregnancy.
Testosterone
Shown to raise testosterone after repair, by about 100 to 120 ng/dL in men with low testosterone. In men with normal levels, the rise did not differ from untreated men.
Compared with before repair, in the same men [9][10][11]; untreated men with varicocele, in 3 studies [10]
The numbers and sources
- Effect
- Across 9 studies of 814 men, testosterone rose 97.48 ng/dL after surgery (95% CI 43.73 to 151.22) [9]. Across 7 studies of men with varicocele, it rose 34.3 ng/dL overall (95% CI 22.57 to 46.04) and 123 ng/dL in men with low testosterone. Against untreated men in 3 studies, the gain in men with low testosterone was 105.65 ng/dL (95% CI 77.99 to 133.32), and men with normal testosterone showed no significant difference (p = 0.36) [10]. Across 18 studies of 1,225 men with low testosterone, levels rose 113.87 ng/dL (95% CI 103 to 124.75) at both under and over 6 months, erectile function scores rose 3.25 points (95% CI 1.49 to 5.01), LH fell slightly (MD -0.28 mIU/mL) and FSH did not change [11].
- Population
- Infertile men with varicocele [9][10]; adults with low testosterone, mostly treated by microsurgical subinguinal repair [11].
- Sources
- [9], [10], [11]
- Caveats
- Most studies compared the same men before and after, without an untreated group [9][11]. The newest review rated studies with observational quality tools [11].
Testicular growth and sperm in teenagers
Shown to raise testicular volume and sperm concentration against observation in boys and young men. Effects on later fatherhood are unknown.
Compared with observation [12]; conservative management [13]
The numbers and sources
- Effect
- Across 98 studies of 16,130 patients aged 7 to 21, treatment raised testicular volume by 1.52 mL (95% CI 0.73 to 2.31) and total sperm concentration by 25.54 million/mL (95% CI 12.84 to 38.25) against observation [12]. Across 9 RCTs, testicular volume rose 3.18 mL (95% CI 1.94 to 4.42) and sperm concentration 25.54 million/mL against conservative management [13].
- Population
- Children and adolescents aged 7 to 21, in 12 RCTs, 47 nonrandomized studies and 39 case series [12]; patients up to 21 in 9 RCTs [13].
- Sources
- [12], [13]
- Caveats
- Neither review found data on paternity or fertility [12][13]. The two reviews report the same sperm estimate, which suggests it rests on the same trials. Evidence was rated low to moderate [13].
Pregnancy and live birth with IVF, ICSI or IUI after repair
One review found higher live birth and pregnancy rates with assisted reproduction when the man's varicocele was repaired first. In men with no sperm, differences were not significant.
Compared with couples in assisted reproduction whose male partner's varicocele was not repaired [5]; men with nonobstructive azoospermia and a varicocele who did not have repair [6]
The numbers and sources
- Effect
- Across 7 studies of 1,241 patients, repair before assisted reproduction was associated with higher live birth rates in men with low sperm counts (OR 1.699) and in men with low or absent sperm combined (OR 1.761), and with higher pregnancy rates in azoospermic men (OR 2.336) and in the combined group (OR 1.760). Live birth after IUI was higher after repair (OR 8.360) [5]. In men with nonobstructive azoospermia using testicular sperm, clinical pregnancy (OR 2.07, 95% CI 0.92 to 4.65) and live birth (OR 2.19, 95% CI 0.99 to 4.83) favored repair without reaching significance [6].
- Population
- Couples undergoing IUI, IVF or ICSI in which the man had a varicocele and low or absent sperm [5]; 468 men with nonobstructive azoospermia and varicocele in 18 studies [6].
- Sources
- [5], [6]
- Caveats
- The review abstract gives no confidence intervals [5]. The studies were observational, and men who chose repair may differ from those who did not. The azoospermia review rated the evidence low to moderate in quality [6].
Microsurgical repair against other surgical methods
Shown to raise pregnancy rates slightly and lower recurrence against other surgical methods, in a Cochrane review rated moderate in certainty.
Compared with other surgical techniques [4]; Palomo, laparoscopic and macroscopic inguinal surgery and radiological embolization, in pooled case series [15]
The numbers and sources
- Effect
- Microscopic subinguinal repair probably raised pregnancy rates against other surgical repairs (RR 1.18, 95% CI 1.02 to 1.36; 12 RCTs, 1,473 couples; moderate certainty), from 10% to between 10% and 14%. It probably lowered recurrence (RR 0.48, 95% CI 0.29 to 0.79; 14 RCTs, 1,565 men), from 1.4% to between 0.4% and 1.1%. Open inguinal and retroperitoneal repair did not differ in pregnancy, recurrence or adverse events across 9 studies [4]. In pooled series of infertile men, spontaneous pregnancy was 41.97% after microsurgical repair, 37.69% after Palomo, 36% after macroscopic inguinal repair, 33.2% after radiological embolization and 30.07% after laparoscopic repair [15].
- Population
- Couples in randomized trials comparing surgical techniques [4]; infertile men with palpable varicocele in 36 studies [15].
- Sources
- [4], [15]
- Caveats
- The case series were not randomized and were reported by technique, so the men treated differ between series [15]. No trial in this comparison reported live birth [4].
Live birth without assisted reproduction
Limited evidence: two trials pointed in opposite directions, so whether repair raises live births is uncertain.
Compared with no treatment [4]
The numbers and sources
- Effect
- Two RCTs comparing surgical or radiological treatment with no treatment reported live birth with differing directions of effect (RR 2.27, 95% CI 0.19 to 26.93; 204 couples; I² 74%; very low certainty) [4].
- Population
- 204 couples in 2 randomized trials in which the man had a varicocele [4].
- Sources
- [4]
- Caveats
- Two trials, very low certainty and a confidence interval running from a large harm to a large benefit. The Cochrane review found no trial data on adverse events or quality of life for this comparison [4].
Varicocele seen only on imaging (subclinical)
Not shown to raise pregnancy rates when a varicocele found only on imaging was repaired. Sperm counts rose slightly in men whose counts were already normal on average.
Compared with men with an unrepaired subclinical varicocele [14]; men with a repaired clinical varicocele [14]
The numbers and sources
- Effect
- Across 13 studies of 1,357 men, repair of a subclinical varicocele was associated with a small rise in sperm density and total motile sperm count against no repair, in men who were on average normospermic beforehand. Pregnancy rates did not rise. Against repair of a clinical varicocele, the gain in total motile sperm count was smaller and the yearly pregnancy rate did not differ [14].
- Population
- Men with subclinical varicocele, detected by imaging and not by examination [14].
- Sources
- [14]
- Caveats
- Risk of bias was high, heterogeneity was high, and studies defined a subclinical varicocele in different ways [14].
Surgery against embolization
Not shown to differ in pregnancy rates between surgery and embolization. Embolization had fewer hydroceles, and reviews disagree on whether it recurs more often.
Compared with radiological treatment [4]; sclero-embolization [16][17]
The numbers and sources
- Effect
- Pregnancy rates were uncertain between surgical and radiological treatment (RR 1.13, 95% CI 0.75 to 1.70; 5 RCTs, 456 couples; low certainty), as was recurrence (RR 1.31, 95% CI 0.82 to 2.08; 3 RCTs) [4]. Across 30 studies, sclero-embolization had more recurrence than high ligation (OR 1.37, 95% CI 1.03 to 1.82), fewer complications overall (OR 0.65, 95% CI 0.47 to 0.91) and fewer hydroceles (OR 0.19, 95% CI 0.10 to 0.35). Sperm concentration did not differ significantly (MD 7.09, 95% CI -0.14 to 14.31) [16]. Across 20 studies, pregnancy, recurrence, overall complications, sperm count and motility did not differ, while normal sperm forms were 2.54 percentage points higher after sclero-embolization [17].
- Population
- Couples in randomized trials [4]; patients in 30 cohort and randomized studies [16]; children, adolescents and adults in 20 studies [17].
- Sources
- [4], [16], [17]
- Caveats
- Most comparisons rest on nonrandomized studies. The two newer reviews disagree on recurrence [16][17].
Practices
Semen quality after heat to the scrotum, sauna and other sources
Shown in one meta-analysis to lower sperm count, motility and normal shape after heat from saunas, heating belts and hot workplaces, in 356 men.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Pooling 9 studies of men exposed to heat from sauna, scrotal heating belts or hot workplaces such as a steel plant, heat exposure lowered semen volume (SMD -0.74, 95% CI -1.11 to -0.36), sperm concentration (SMD -1.07, 95% CI -1.42 to -0.72), total sperm count (SMD -1.52, 95% CI -2.96 to -0.08), motility (SMD -1.93, 95% CI -2.83 to -1.04) and normal morphology (SMD -2.41, 95% CI -3.30 to -1.52) [44]. In 8 men taking a sauna at 80°C to 90°C for 30 minutes a day, sperm movement speed fell after 2 weeks and returned to baseline within 1 week of stopping. Semen volume, sperm count, motility and morphology did not differ from control values [45].
- Population
- 356 men in 9 studies from Iran, Italy, Thailand, China and Egypt, two of them sauna studies [44]; 8 healthy men [45].
- Sources
- [44], [45]
- Caveats
- The meta-analysis pooled very different heat sources, and only two of its studies used a sauna [44]. In the sauna studies, men served as their own controls. Fertility itself was not measured.
Sperm count and motility
One small study found sperm count and motility fell after 3 months of twice-weekly saunas in 10 men, and recovered fully within 6 months of stopping.
The numbers and sources
- Effect
- After two 15-minute sessions a week at 80°C to 90°C for 3 months, sperm count and motility were strongly impaired (P < 0.001). The share of sperm with normal mitochondrial function fell from 76.8% to 54.0%, and with normal chromatin condensation from 70.7% to 63.6%. Sex hormones did not change. All effects had reversed 6 months after the sessions ended [29].
- Population
- 10 men with normal sperm counts at the start [29].
- Sources
- [29], [35]
- Caveats
- Ten men, no control group, and none had abnormal sperm at baseline. A systematic review of 40 sauna studies with 3,855 participants found this was the only study reporting an adverse health outcome [35]. Fertility itself was not measured.
Daily life
Semen quality after quitting
One study found semen volume, sperm concentration and total sperm count rose 3 months after quitting in 48 heavy smokers at an infertility clinic.
Compared with men who kept smoking [23]
The numbers and sources
- Effect
- In 90 infertile men who smoked at least 20 cigarettes a day, the 48 who quit had higher semen volume (2.48 to 2.90 mL, P = 0.002), sperm concentration (18.45 to 22.64 million per mL, P = 0.001) and total sperm count (45.04 to 65.1 million, P < 0.001) at least 3 months later. Motility and morphology also rose, but not significantly. The 42 men who kept smoking were retested over the same interval as controls [23].
- Population
- 90 men at an infertility clinic, mean age 34.7, smoking a mean 30 cigarettes a day for a mean 8.3 years [23].
- Sources
- [23]
- Caveats
- Not randomized, since the men chose whether to quit. The changes are reported within the group that quit. Pregnancy was not measured.
Lower sperm count and quality
Linked in two meta-analyses to lower sperm counts and more abnormally shaped sperm in men who smoke, with larger effects in moderate and heavy smokers.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Across 20 studies (5,865 men), smoking was linked to lower sperm count (MD -9.72 million per mL, 95% CI -13.32 to -6.12), motility (MD -3.48 points, 95% CI -5.53 to -1.44) and normal morphology (MD -1.37 points, 95% CI -2.63 to -0.11). Effects were larger in infertile men than in the general population, and in moderate and heavy smokers than in mild smokers [24]. Across 16 studies of infertile men, oligozoospermia was more common in smokers (RR 1.29, 95% CI 1.05 to 1.59), as were morphological defects (MD 2.44, 95% CI 0.99 to 3.89). Motility (RR 1.42, 95% CI 0.97 to 2.09) and reproductive hormones did not differ [25].
- Population
- 5,865 men from fertility and urology clinics and andrology laboratories [24]; 10,823 infertile men, 5,257 of them smokers [25].
- Sources
- [24], [25]
- Caveats
- Observational studies, open to confounding by other habits. The two reviews disagree on motility. Neither measured pregnancy.
Sperm count and quality
Mixed results: pooled studies linked cannabis use to slightly poorer sperm shape but not to count or motility, while single large studies found lower or higher counts in users.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Across 9 studies of 4,014 men, 44.9% of cannabis users and 24.5% of non-users had an impaired semen measure, a difference that was not significant (RR 1.159, 95% CI 0.840 to 1.599). FSH was slightly lower in users (SMD -0.142) [15]. Across 18 studies of 5,766 men, users had lower normal sperm morphology than non-users (MD -1.02, 95% CI -1.93 to -0.10), and sperm concentration, total count, semen volume and motility did not differ [12]. In 1,215 young Danish men, use more than once a week was linked to 28% lower sperm concentration (95% CI -48 to -1) and 29% lower total count than no use, and 52% lower concentration when combined with other drugs [11]. In 662 men at a US fertility center, men who had ever smoked marijuana had higher sperm concentration than men who never had (62.7 against 45.4 million/mL) [16].
- Population
- Men in population-based and clinic studies [15][12]; 1,215 Danish men aged 18 to 28 at military fitness exams [11]; 662 subfertile US men [16].
- Sources
- [15], [12], [11], [16]
- Caveats
- Observational, with use self-reported. Cannabis users differ from non-users in tobacco, alcohol and other drug use, which studies adjusted for unevenly. Semen measures are not pregnancies.
Time to pregnancy and live birth when the man uses cannabis
Not linked to longer time to pregnancy when men used cannabis, in two population studies. A fertility clinic study unexpectedly linked male use to more live births.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In a US national survey of 758 men trying to conceive, time to pregnancy did not differ between daily users and never users (time ratio 1.08, 95% CI 0.79 to 1.47) [13]. In 1,125 North American couples, fecundability did not differ when the man used cannabis less than weekly (FR 0.87, 95% CI 0.66 to 1.15) or weekly or more (FR 1.24, 95% CI 0.90 to 1.70) against no use [17]. In couples having IVF or related treatment, those in which the man currently smoked marijuana had a higher adjusted live birth rate than those in which he had never or only previously smoked (48% against 29%, p = 0.04) [18].
- Population
- 758 men and 1,076 women trying to conceive in the US National Survey of Family Growth [13]; 4,194 women and 1,125 male partners in a preconception cohort [17]; 421 women and their partners in 730 assisted reproduction cycles, 23 men current smokers [18].
- Sources
- [13], [17], [18]
- Caveats
- Observational, with self-reported use, and men who use cannabis differ from non-users in tobacco, alcohol and other habits. The clinic finding rests on few exposed men and may be chance [18]. The survey measured time to pregnancy retrospectively [13].
Food and drink
Semen quality with regular drinking
Linked to lower semen volume and fewer normally shaped sperm in 15 studies, mostly in daily drinkers, and to lower sperm counts from 5 units a week.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Across 15 cross-sectional studies (16,395 men), men with no or low alcohol intake had 0.25 mL more semen (95% CI 0.07 to 0.42) and 1.87 points more normally shaped sperm (95% CI 0.86 to 2.88). Differences were larger between occasional and daily drinkers than between never and occasional drinkers [29]. In 1,221 Danish men aged 18 to 28, sperm concentration, total count and normal morphology were lower with higher typical weekly intake, from 5 units a week and most at more than 25. Men drinking over 40 units a week had 33% (95% CI 11% to 59%) lower sperm concentration than men drinking 1 to 5. Binge drinking was not independently linked to semen quality [30].
- Population
- 16,395 men in 15 cross-sectional studies [29]; 1,221 young men at military fitness examinations, 2008 to 2012 [30].
- Sources
- [29], [30]
- Caveats
- All the studies were cross-sectional, with self-reported drinking, so they cannot show cause. Drinkers differ from nondrinkers in other habits. Neither source measured pregnancy.