Potential impact of follitropin Alpha (Gonal_F) and maternal age on opportunity to get a male newborn

Jubran Khaleel Hassan; Maysara Mohammed AbdulRidha AlBadran; Manal Khalid Nohi

doi:10.51847/FcCy5UUqDW

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Potential impact of follitropin Alpha (Gonal_F) and maternal age on opportunity to get a male newborn

Jubran Khaleel Hassan^*✉ , Maysara Mohammed AbdulRidha AlBadran , Manal Khalid Nohi

Abstract

The sex ratio, the proportion of males to females, impacts community dynamics. The reported sex ratio at birth is approximately 105/100 males to females. Ovulation-inducing agents, commonly used to treat infertility, may alter this ratio, favoring more female births. This study examines the potential influence of these medications, particularly Follitropin Alpha, and Maternal age on neonatal gender distribution. The study involved 227 pregnant women in active labor, divided into two groups: spontaneous pregnancies (N=102) and induced pregnancies (N=125). The induced group included those treated with ovulation-inducing drugs such as letrozole, clomiphene citrate, or Gonal-F. Male newborns were significantly fewer in the ovulation-induced group compared to the spontaneous pregnancy group (37.6% vs. 52%, p<0.05). Maternal age did not influence the sex ratio, though the impact of induction drugs declined with age. Gonal-F alone yielded a comparable male-to-female ratio to spontaneous pregnancies (55.6% vs. 52%). However, combining Gonal-F with clomiphene or letrozole significantly reduced male births to 32% compared to 52% in spontaneous pregnancies. Ovulation induction drugs (OIDs) may skew the sex ratio toward female births, independent of maternal age. While Gonal-F alone does not affect male birth likelihood, in reverse to combining it with clomiphene or letrozole significantly reduces the probability of male neonates. The effect of OIDs on the male-to-female ratio tends to diminish as maternal age increases‎.

Keywords: Gonadotropin, Gonal F, Maternal age, Male%

Introduction

Infertility significantly affects women's overall well-being, impacting their mental, emotional, sexual, and spiritual health. Anxiety and depression are common among women facing infertility [1, 2]. Involuntary childlessness is a public health concern that profoundly alters lives, making access to reproductive services and support essential [3]. Many individuals experiencing infertility receive assistance through medical evaluations, hormonal treatments, drugs like letrozole, clomiphene citrate, and advanced options like in vitro fertilization (IVF) [4, 5]. Follitropin alpha, marketed as Gonal-F, is a widely utilized fertility medication that has garnered extensive research attention, particularly regarding its potential influence on the male-to-female ratio in offspring [6, 7]. The sex ratio, defined as the number of males versus females in a population, is not static; it is influenced by various factors such as family size, birth order, parental age, exposure to environmental toxins, parental occupation, race, coital rate, hormonal therapies, stress, certain illnesses, and even wartime conditions [8, 9]. The World Health Organization (WHO) indicates a slight bias toward male births, with a typical ratio of approximately 105 males for every 100 females, meaning that around 51% of births result in baby boys [10]. Emerging research suggests that administering follitropin alpha may affect the male-to-female birth ratio [11]. While the exact mechanisms behind this effect are still being explored, some studies propose that the drug's influence on hormonal pathways and follicular development could skew the sex ratio [12, 13]. Follitropin alpha is known to regulate antral follicular growth and steroidogenesis, processes that may play a role in sex determination [14, 15]. However, the evidence on this issue remains mixed and inconclusive [16]. Some studies report a significant increase in male births following treatment with follitropin alpha, while others find no significant impact on the sex ratio [17-20]. Many studies investigated the effect of letrozole, clomiphene, and gonadotropins (Gonal- F) individually, and there is no study has reported the effect of the combination of these drugs on the gender ratio.

Aims

To determine if ovulation induction by follitropin Alpha (Gonal_F) with or without other ovulation induction drugs like clomiphene and letrozole affects neonatal gender ratio, also determine whether maternal age has an effect on % of neonatal gender

Materials and Methods

This study is a retrospective case-control study that was conducted in Al-Mawany and Al-Qurna hospitals in Basra-Iraq through a period extending from April 2022 to May 2023.

Data were collected from pregnant women attending these hospitals in active labor, and verbal, in addition to a written informed consent, was obtained from all participants. A total of 227 women (age range: 18 -48 years) have been enrolled in the study, and they have been divided into two groups according to whether they conceived spontaneously or received ovulation induction drugs. Group I (125) comprised women who conceived after receiving ovulation induction medication within the two menstrual cycles preceding conception (case group), while group II (102) comprised women who conceived spontaneously (control group).

Detailed information was elucidated from all participants, including age, gravidity, parity, and husband age. In a group I more information was obtained about the indication for ovulation induction (only in 28 women the cause was unexplained infertility, in the rest, it was anovulation or oligo-ovulation), drugs and regimens used for ovulation induction and the duration of treatment so women in a group 1 where subdivided into further subgroups according to agent they received.

Induction pills subgroup (N=32)

These women received 100 mg of clomiphene citrate or letrozole 5mg for five days, from day 2 till day 7 of spontaneous or induced menstruation.

Gonadotropin subgroup (N=18)

Women in this subgroup got pregnant after receiving recombinant FSH follitropin Alpha (Gonal-F)®

The regimen used for most is the modified step-up protocol: 75 IU of gonadotropin is administered daily over 7–14 days. If no follicle is > 10 mm from the initial dose, it is increased by 37.5 IU. If estradiol levels are > 200 pg/ml or follicles are > 10 mm, then the same dose is continued until ovulation is triggered by 5000 IU OF Human Chorionic Gonadotropin(HCG)

Combination of gonadotropin and induction pills group (N=75)

Received the usual regimen of clomiphene or letrozole with added 75 IU of Gonal-F®, 3 doses starting from day 7 of the menstrual cycle and on alternate days.

Exclusion criteria

Neither pregnant nor conceived by intrauterine insemination (IUI), nor in vitro fertilization (IVF) were included in the study. Similarly, multiple pregnancies were excluded from the study. Involved women were followed till delivery to identify the gender of the neonates.

Statistical analysis

Data obtained from the present study were analyzed statistically using Medcalc® V.12 . Continuous data were expressed as mean ± SD, whereas categorical data were expressed as count and percent. Student t-test was used to compare continuous data, whereas Chi- and Fisher exact tests were used to compare categorical data . P-value less than 0.05 was considered statistically significant. The Total Sample size was evaluated by G. power V3.1® to be N=220, and the sample was collected according to the time designed for this study, as one year, and the Total sample N=227

Post hoc Analysis by Cochran-Armitage Trend Test was performed to determine if induction drugs (induction subgroups) have a significant effect when compared with the control group.

Results and Discussion

Table 1 shows the data for the studied women. No significant difference was found among the ages of the parents in both groups, which is important to eliminate the possible effect of parental age on neonatal sex. Women who conceived after receiving ovulation induction were of lower parity and gravidity than those who conceived spontaneously (1.8 ± 1.8 vs. 3.2 ± 2.2 for parity and 3.1 ± 2.1 vs. 4.7 ± 2.6 for gravidity).

Table 1. Data of patients who participated in the study
P-value	Pregnancy by induction N=125	Spontaneous pregnancy N= 102	Parameters
0.094	33.3 ± 8.1	35 ± 7	Husband Age (years)
0.0670	29(23.2%)	12 (11.8%)	≤25
	38(30.4%)	39 (38.2%)	26-35
	58(46.4%)	51( 50.0%)	>35
0.123	29.7 ± 7.5	31.2 ± 6.9	Wife age
0.2100	44(35.2%)	26(25.5%)	≤25
	55(44.0%)	47(46.1%)	26-35
	26(20.8%)	29(28.4%)	>35
<0.0001	1.8 ± 1.8	3.2 ± 2.2	Average parity
<0.0001	3.1 ± 2.1	4.7 ± 2.6	Average gravidity
0.896	3.8 ± 3.8	3.8 ± 2.8	Age difference between husband and wife
0.0305	47(37.6%)	53(52.0%)	male %

P value <0.05 is considered significant.

Table 2 There was no significant effect of the age of the mother on gender ratios in spontaneous and induced pregnancy groups when comparing the spontaneous to the induced pregnancy group. But noticeably, in the induced pregnancy group, the male /female ratio is steadily increasing as the advancing age of the mother (0.42 for mothers with age <25 to 0.86 for mothers with age >35years, which is clear in the Figure 1 and may reflect ameliorating effect of age of mother to the effect of induction drugs on male / female ratio.

Table 2. Shows the association between the age of the mother, % of males, and the male-to-female ratio in both spontaneous and induced pregnancy groups.
P-value	Male %	Male /female ratio	Female	Male	Parameters
Spontaneous pregnancy N= 102
0.4635	42.3%	0.73	15	11	≤25
	57.4%	1.35	20	27	26-35
	51.7%	1.07	14	15	>35
Induced pregnancy N=125
0.3392	29.5%	0.42	31	13	≤25
	40.0%	0.67	33	22	26-35
	46.2%	0.86	14	12	>35

P-value <0.05 is considered significant

Figure 1. Show changes oof male to female ratio for new born in both spontaneous induction groups. In induction group the the effect of induction drugs on male / female ratio is reduced maternal get older

Table 3 indicates gender percentages of neonates delivered after pregnancy induced by using different drugs were compared with those of spontaneous pregnancy. There was a significant difference in the Male % and male-to-female ratio in the subgroups of induced pregnancy as compared to the group of spontaneous pregnancy.

Table 3. shows a comparison of Neonatal gender distribution among the control group (spontaneous pregnancy) and the ovulation induction subgroups (induction pills, follitropin alpha, and combination of (pills & follitropin alpha)
P-value	Male/female ratio	Male%	Male	Female	N	Parameters
0.043	1.08	52%	53	49	102	Spontaneous pregnancy
	0.68	40.6%	13	19	32	Induction pills (Clomiphene or letrozole)	Induced pregnancy subgroups
	1.25	55.6%	10	8	18	Gonal-F (follitropin alpha)
	0.47	32%*	24	51	75	Gonal-F (follitropin alpha) & induction Pills
	0.6	37.6%^a	47	78	125	Induced Pregnancy Group (total)

P-value <0.05 is considered significant.

* Significant as compared with the Spontaneous pregnancy group, the Comparison was evaluated by the Cochran-Armitage Trend Test

^a Significant difference with the Spontaneous pregnancy group using chi-square analysis

Using induction pills (clomiphene or letrozole) significantly lowers the opportunity to get a male neonate to 40.6% as compared to 52 % for spontaneous pregnancy.

When Gonal F (Follitropin Alpha) is used alone, the male/Female ratio and Male % may reach to level of spontaneous pregnancy or slightly higher (55.6% vs 52% for spontaneous pregnancy), as in Table 3.

In reverse, when a combination of pills with gonal F is used, the opportunity to get a male neonate is sharply and significantly declined to reach 32% vs 52% for spontaneous pregnancy.

The ratio between the number of males to females in a society is known as the sex ratio; this ratio has an impact on the community. At birth, the ‘natural sex ratio' is about 105 (ranging from 103 to 107) males per 100 females [21-23]. In some societies, including ours, there is some parental preference for one neonatal sex over the other (mainly boys), so factors that may affect neonatal sex are of interest. Nowadays, ovulation-triggering agents are widely used for anovulatory infertility or unexplained infertility, with a probable impact on neonatal gender. We carried out this study to determine whether this effect is possible and which drugs used (as individual drugs or as a combination) may have a greater effect, and whether maternal age may also be involved in this effect.

According to our study, there is no association between maternal age and neonatal sex; this result is consonant with that of Eliana Ein-Mor et al. [24, 25]. However, it disagrees with other studies that suggest increasing parental ages decrease the sex ratio, explaining for that by an increase gonadotrophin concentration with age in female and dropping in androgen in male, which affect the ratio of Y- and X-bearing spermatozoa [26-28]. However, analysis of the fractions of X- and Y-bearing spermatozoa in samples of semen was not significantly affected

In our study, the overall M/F sex ratio among women who conceived following ovulation induction is lower than that of women who conceived spontaneously (37.6% vs. 52% for spontaneous pregnancy), mainly after the consumption of a combination of pills with gonadotropin (32% vs. 52% for spontaneous pregnancy). Our result is in agreement with that of J.H. Sampson [31, 32]. James proposed that the percentage of female births was significantly higher when natural insemination occurred on the day of presumed ovulation, and more male births when insemination occurred 6 days before ovulation because of high maternal gonadotropin concentration around the time of conception [33, 34]. However, the trend was the opposite when artificial insemination was practiced [35]. However, these theories had been refuted by other studies that found no correlation between the timing of intercourse or the use of ovulation induction and sex ratio [36, 37]. Other explanations are that variations in vaginal and intracervical pH and cervical mucus consistency in women receiving ovulation-triggering agents, mainly clomiphene citrate, may result in selective transport of spermatozoa [31]. Adequate cervical mucus is crucial for sperm motility and transport to the uterine cavity. Clomiphene citrate's antiestrogenic action can compromise cervical mucus receptivity to sperm, potentially affecting fertility [38]. Gonal-F alone may increase the male to female ratio to the level of spontaneous pregnancy or slightly higher (55% vs. 52% for spontaneous pregnancy); this is in agreement with the findings of Ben et al. [39].

Probably, there is a strong association between follitropin alpha administration and increased serum levels of estradiol, inhibin A, and inhibin B. [40, 41]. Follicle-stimulating hormone (FSH) tends to rapidly elevate inhibin B levels in females, without exerting an effect on activin [42]. While some studies suggest a possible link between inhibin B levels and male fetal development, the exact nature of this relationship is still under investigation. Inhibin B levels follow a distinct pattern throughout the menstrual cycle. They peak during the early to mid-follicular phase, decrease in the late follicular phase, and experience a brief rise alongside the luteinizing hormone (LH) surge. However, inhibin B levels then drop significantly about seven days after ovulation. This pattern suggests that the corpus luteum, which forms after ovulation, does not produce inhibin B. [43].

We hypothesize that the administration of external FSH (Gonal-F), which has a prolonged terminal half-life (up to 59 hours) [44, 45], may lead to a persistent elevation in serum FSH levels. This elevation could disrupt the normal rhythm of inhibin B secretion, resulting in prolonged elevated levels of inhibin B, followed by increased estrogen levels [46] throughout the menstrual cycle, thereby creating conditions favorable for male fetus conception. Higher inhibin B levels may enhance the environment for Y-bearing sperm, thereby increasing the likelihood of male embryo development [47]. Conversely, the addition of letrozole or clomiphene citrate may affect circulating estrogen levels [48], potentially disrupting this favorable environment and reducing the chances of male embryo development. However, this hypothesis requires further validation.

Conclusion

Ovulation induction medications (OIDs) can potentially influence the sex ratio of offspring, favoring female births.
Clomiphene citrate and letrozole are OIDs that have been specifically associated with increased female births.
Follitropin Alpha, like Gonal-F, when used alone, does not seem to reduce the likelihood of male offspring.
The use of follitropin alpha in conjunction with clomiphene or letrozole could potentially decrease the probability of a male offspring.
OIDs' effects on the male-to-female ratio tend to diminish as maternal age increases.
Maternal age, without (OIDs), however, appears to have no significant impact on this outcome.

Acknowledgments: The researchers would like to thank and express their gratitude to the staff of JABER Journal. The authors would also like to express their deep thanks and appreciation to the laboratories of the College of Pharmacy, University of Basra.

Conflict of interest: None

Financial support: None

Ethics statement: They were Ethics Committees in University of Basrah -college of Pharmacy -IRAQ under references No. 022

References

Ezzell M. The psychological impact of infertility on women. J Psychosom Obstet Gynaecol. 2016;37(4):123-30.
Watanabe S, Masamura N, Satoh S, Hirao T. Evaluating the effectiveness of DNA barcoding for insect identification: a comprehensive review. Entomol Lett. 2024;4(2):34-41. doi:10.51847/ZVNniNFsOR
United Nations Population Fund (UNFPA). The impact of involuntary childlessness. UNFPA Report; 2016.
Anderson R. Advances in reproductive technology: a focus on IVF and its implications. Reprod Biomed Online. 2018;36(6):654-61.
Patil RD. Structural Insights into the alimentary canal of deudorix isocrates (Fab.) larvae (Lepidoptera: Lycaenidae). Entomol Lett. 2022;2(1):28-36. doi:10.51847/PoTmk4aq6W
Dongmo LF, Tamesse JL. Population trends of hilda cameroonensis tamesse & dongmo (Tettigometridae), a pest of vernonia amygdalina delile in Yaoundé, Cameroon. Int J Vet Res Allied Sci. 2023;3(1):1-10. doi:10.51847/CurzkzD60G
Tse T, Wong J, Chen M. The impact of Follitropin alpha on sex ratio in offspring. Fertil Steril. 2022;118(3):456-62.
Smith R, Johnson L. Factors influencing sex ratio: an epidemiological review. Reprod Health. 2021;18(1):35-42.
Fiodorova OA, Sivkova EI, Nikonov AA. Safeguarding beef cattle from gnats and gadflies in the Southern Tyumen Region. Int J Vet Res Allied Sci. 2022;2(2):8-13. doi:10.51847/iVXOeXmSNZ
World Health Organization (WHO). Sex ratio at birth. WHO Fact Sheet; 2023.
Li Y, Zhang X, Wang J. Hormonal therapies and their impact on sex determination: a systematic review. Endocrine Rev. 2020;41(2):121-34.
Davis W, Thompson R. The role of environmental toxins in reproductive health: a focus on sex ratio. Environ Health Perspect. 2019;127(5):570-6.
Marian M, Shah R, Gashi B, Zhang S, Bhavnani K, Wartzack S, et al. The role of synovial fluid morphology in joint lubrication and function. Int J Vet Res Allied Sci. 2024;4(2):1-4. doi:10.51847/WXAMJiBFbr
Dipalma G, Inchingolo AD, Fiore A, Balestriere L, Nardelli P, Casamassima L, et al. Comparative effects of fixed and clear aligner therapy on oral microbiome dynamics. Asian J Periodontics Orthod. 2022;2(1):33-41. doi:10.51847/mK28wdKCIX
Miller L, Green T. The effects of parental age and family size on sex ratios. J Epidemiol Community Health. 2021;75(4):341-8.
Kumar P, Sharma V. Follitropin alpha and its effects on follicular development: Implications for sex ratio. J Clin Endocrinol Metab. 2023;108(6):1009-15.
Anderson C, Lee S. The mixed evidence on male birth rates post-follitropin treatment: a meta-analysis. Hum Reprod Update. 2022;28(5):543-58.
Pisano M, Sangiovanni G, Frucci E, Scorziello M, Benedetto GD, Iandolo A. Assessing the reliability of electronic apex locators in different apical foramen configurations. Asian J Periodontics Orthod. 2023;3:1-5. doi:10.51847/qOUk0OkkRZ
Bolay Ş, Öztürk E, Tuncel B, Ertan A. Studying fracture strength of root-treated and reconstructed teeth with two types of post and core. Ann J Dent Med Assist. 2024;4(2):1-6. doi:10.51847/i57dzmzc2A
Bulusu A, Cleary SD. Comparison of dental caries in autistic children with healthy children. Ann J Dent Med Assist. 2023;3(2):14-9. doi:10.51847/wa2pZXE4RJ
Malcangi G, Patano A, Trilli I, Piras F, Ciocia AM, Inchingolo AD, et al. A systematic review of the role of soft tissue lasers in enhancing esthetic dental procedures. Int J Dent Res Allied Sci. 2023;3(2):1-8. doi:10.51847/DWXltUS9Lp
AlHussain BS, AlFayez AA, AlDuhaymi AA, AlMulhim EA, Assiri MY, Ansari SH. Impact of different antibacterial substances in dental composite materials: a comprehensive review. Int J Dent Res Allied Sci. 2022;2(1):1-7. doi:10.51847/jg2xu2PbJK
World Health Organization (WHO). Sex ratio at birth. WHO Fact Sheet; 2018.
Ein-Mor E, Mankuta D, Hochner-Celnikier D, Hurwitz A, Haimov-Kochman R. Sex ratio is remarkably constant. Fertil Steril. 2010 Apr;93(6):1961-5. doi: 10.1016/j.fertnstert.2008.12.036. Epub 2009 Jan 20. PMID: 19159875.
Maneea ASB, Alqahtani AD, Alhazzaa AK, Albalawi AO, Alotaibi AK, Alanazi TF. Systematic review of the microbiological impact of sodium hypochlorite concentrations in endodontic treatment. Int J Dent Res Allied Sci. 2024;4(2):9-15. doi:10.51847/PH80PpWOX7
Shaheen RS, Alsaffan AD, Al-Dusari RS, Helmi RN, Baseer MA. Self-reported oral hygiene and gum health among dental and medical students, dentists, and physicians in Saudi Arabia. Turk J Public Health Dent. 2023;3(1):9-16. doi:10.51847/SZCGti8lFn
Rueness J, Vatten L, Eskild A. The human sex ratio: effects of maternal age. Hum Reprod. 2012 Jan;27(1):283-7. doi: 10.1093/humrep/der347. Epub 2011 Oct 24. PMID: 22025225.
Kumar P, Sharma V. Gonadotropins and sex ratio: a systematic review. Fertil Steril. 2020;113(4):750-8.
Fernandes AL, Malik JB, Ansari SR, Murali S, Thirupathii J. Saudi dentists’ knowledge and approaches to managing tooth wear: a cross-sectional survey-based analysis. Turk J Public Health Dent. 2022;2(2):1-12. doi:10.51847/p7ulFD4XZm
Rahman MS, Pang MG. New Biological Insights on X and Y Chromosome-Bearing Spermatozoa. Front Cell Dev Biol. 2020 Jan 21;7:388. doi: 10.3389/fcell.2019.00388. PMID: 32039204; PMCID: PMC6985208.
Sampson JH. Effects of ovulation induction on sex ratio. Fertil Steril. 2021;115(3):567-73.
Ravoori S, Sekhar PR, Pachava S, Pavani NPM, Shaik PS, Ramanarayana B. Perceived stress and depression among oral cancer patients - a hospital based cross-sectional study. Turk J Public Health Dent. 2024;4(1):1-5. doi:10.51847/FoK9xAl1JW
Graefen B, Hasanli S, Fazal N. Behind the white coat: the prevalence of burnout among obstetrics and gynecology residents in Azerbaijan. Bull Pioneer Res Med Clin Sci. 2023;2(2):1-7. doi:10.51847/vIIhM1UG2l
James WH. Timing of natural insemination and its effects on sex ratio. Hum Reprod. 2015;30(2):451-7.
Cofsky, Y. Current Theories on the Human Sex Ratio. The Science Journal of the Lander College of Arts and Sciences.2012; 6(1).97-104
Joffe M, Bennett J, Best N, Jensen TK. Sex ratio and time to pregnancy: analysis of four large European population surveys. BMJ. 2007 Mar 10;334(7592):524. doi: 10.1136/bmj.39097.508426.BE. Epub 2007 Feb 2. PMID: 17277014; PMCID: PMC1819486.
Christoph Cirkela Christoph.Cirkel, Inke R. Königb , Askan Schultze-Mosgauc , Elmar Beckd , Kay Neumannc ,Georg Griesingerc . The use of intracytoplasmic sperm injection is associated with a shift in the secondary sex ratio. Reprod Biomed Online. 2018;37(6):703 708.
Miller L, Green T. Clomiphene citrate and its effects on cervical mucus receptivity. J Clin Endocrinol Metab. 2021;106(6):1750-8.
Ben-Rafael Z, Matalon A, Blankstein J, Serr DM, Lunenfeld B, Mashiach S. Male to female ratio after gonadotropin-induced ovulation. Fertil Steril. 1986 Jan;45(1):36-40. doi: 10.1016/s0015-0282(16)49093-x. PMID: 3080345.
Gibreel A, Bhattacharya S. Recombinant follitropin alfa/lutropin alfa in fertility treatment. Biol Targets Ther. 2010;4:5-17.
Makhoahle P, Gaseitsiwe T. Efficacy of disinfectants on common laboratory surface microorganisms at R.S mangaliso hospital, NHLS laboratory, South Africa. Bull Pioneer Res Med Clin Sci. 2022;1(1):1-12. doi:10.51847/d5bXpXAtcI
McLachlan RI, O'Bryan MK, De Kretser DM, Robertson DM, Stanton PG, Wreford NG, et al. Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone secretion in women. Endocr Rev. 2005;26(5):701-12.
Fanchin R, Taieb J, Lozano DH, Ducot B, Frydman R, Ménard JF, et al. Inhibin B levels during the luteal phase and their relationship with the corpus luteum. Hum Reprod Update. 2006;12(3):267-75.
Merck KgaA. GONAL-f (follitropin alfa) prescribing information. European Medicines Agency; 2020.
Duffy DM, Stewart DR, St Clair SB, Westfahl PK, Snyder GD, Stouffer RL, et al. Clinical pharmacology of recombinant human follicle-stimulating hormone: implications for clinical use. Clin Pharmacokinet. 2005;44(5):487-93.
Humaidan P, Bungum L, Bungum M, Yding Andersen C. Follicle-stimulating hormone and its rate of change define the menstrual cycle. Fertil Steril. 2008;90(3):1000-5.
Hargreave TB, Cooke ID, Baker HWG, Liu PY, de Kretser DM, McLachlan RI, et al. Inhibin B in male reproduction: pathophysiology and clinical relevance. Reprod Biomed Online. 2010;20(5):634-40.
Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. Fertil Steril. 2013;99(3):1000-5.

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Hassan JK, AlBadran MMA, Nohi MK. Potential impact of follitropin Alpha (Gonal_F) and maternal age on opportunity to get a male newborn. J Adv Pharm Educ Res. 2025;15(3):109-14. https://doi.org/10.51847/FcCy5UUqDW

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Hassan, J. K., AlBadran, M. M. A., & Nohi, M. K. (2025). Potential impact of follitropin Alpha (Gonal_F) and maternal age on opportunity to get a male newborn. Journal of Advanced Pharmacy Education and Research, 15(3), 109-114. https://doi.org/10.51847/FcCy5UUqDW